P1469: LONGITUDINAL SICKLE CELL DISEASE COHORT-STUDY: IN CHILDREN WITH SPLENIC SEQUESTRATION HISTORY OR HYPERSPLENISM, PARTIAL VS TOTAL SPLENECTOMY BEFORE STEM CELL TRANSPLANTATION PRESERVES SPLEEN FUNCTION
Authors: F. Bernaudin, C. Arnaud, A. Kamdem, C. Pondarré, I. Hau, N. Bayani, M. Kuentz, E. Gluckman, R. Peffault de Latour, N. Dhédin, H. Lezeau, J.-H. Dalle
Journal: HemaSphere (2022)

Background: The presence of Howell-Jolly bodies (HJB) is associated with splenic dysfunction that appears progressively during aging or after splenectomy in patients with sickle cell disease (SCD). Improvement of splenic function has been found in several SCD patients after transplantation, prompting our team to propose a partial splenectomy prior to transplantation to patients with hypersplenism and available matched-sibling donor (MSD) Aims: To evaluate splenic function from birth to adulthood, the impact of intensive treatments: hydroxyurea (HU), chronic transfusion (CT), transplantation and compare the impact of splenectomy (partial/total) in SCD patients when transplanted or not Methods: Scores for HJB (0 to 3) were assessed on blood smears in the pediatric Créteil SCD-cohort and prospectively recorded at each annual check-up. This study included 4103 annual check-ups with available HJB score and all other biological parameters: Hb, HbA%, HbS%, HbF%, platelets etc. performed in 907 SCD patients (111 SC, 47 Sb+, i.e 158 SC/Sb+) and (725 SS, 21 Sb0 and 3 SDPunjab, i.e. 749 SCA-children) from January 1991 to January 2014 Results: HJB scores increased with aging in SCD patients, but were significantly lower in SC/Sb+ than in SS/Sb0 patients at each assessment age, P<0.001 (Figure 1). Multivariate logistic regression analysis showed that genotype (SCA vs SC/Sb+), splenectomy history and age at check-up were all strong significant (P<0.001) and independent risk factors for HBJ score >1 (>0.2% RBCs containing HJBs). Among 749 SCA (SS/Sb0) children, 86 were splenectomized at the mean age (SD) of 6.4 years (3.9). As expected, HJB score was significantly higher at check-ups in splenectomized than in non-splenectomized SCA-patients, P<0.001 (Figure 2). Among SCA-children, 138 were transplanted with MSD at a mean age (SD) of 9.0 years (4.9). At each age of assessment, HJB score was strongly significantly lower in transplanted than in non-transplanted children (p<0.001), (Figure 3) and the score in transplanted children was significantly positively correlated with the age at transplant (r=0.335; p=0.002). In non-splenectomized SCA-children, mean (SD) HJB scores were unexpectedly significantly higher (P<0.001) in patients on HU 1.39 (0.91) than in not-intensified 1.11 (0.82), in those on CT 1.09 (0.86) and in transplanted children 0.35 (0.7) (Figure 4). Multivariate analysis showed that on HU, HbF and MCV were inverse independent significant risk factors for HBJ score>1 (p<0.001). Seven children with splenic sequestration history or hypersplenism and available MSD-donor had partial splenectomy before transplant performed at mean (SD) age of 5.9 years (1.8). The mean (SD) HJB score was 1.83 (1.2) before and was null after transplant in the seven children Image:Summary/Conclusion: The higher number of RBCs containing HJBs observed on HU is intriguing and could be related to altered erythropoisesis kinetics, drug-induced genotoxicity or altered splenic function because of drug-induced high MCV. This cohort study clearly shows that splenic dysfunction increases with aging in SCA children and that stem cell transplantation allows to preserve splenic function, especially if the transplant is performed early. In children with indication of splenectomy for recurrent splenic sequestrations or hypersplenism who have an available MSD, the present study suggests that partial splenectomy just before stem cell transplantation may be useful to preserve splenic function.